Figure 2.

Diagram indicating the points in the AMPAR trafficking pathway that are known to be regulated by actin-based protein machinery. AMPARs are endocytosed at endocytic zones adjacent to the PSD in a process that involves the modulation of F-actin turnover, and the actin-biding proteins CPG2, Arc, and the Arp2/3 inhibitor PICK1. AMPAR-containing endocytic vesicles are transported away from the plasma membrane along F-actin tracks by the minus-end directed actin motor protein myosin VI. In the recycling endosome, AMPARs associate with actin filaments via RIL and the plus-end directed motor protein myosin Va, which direct AMPAR traffic towards the plasma membrane. In addition, AMPAR-containing recycling endosomes associate with the plus-end directed motor protein myosin Vb via Rab11-FIP2, which pulls the endosome into the spine to increase the availability of AMPARs for subsequent plasma membrane insertion. PICK1 restricts AMPAR recycling back to the plasma membrane in a process that is likely to involve F-actin turnover. The insertion of AMPARs into the plasma membrane requires the activity of ADF/cofilin and the actin-binding protein 4.1N. Red arrows represent trafficking events that are involved in reducing AMPAR surface expression, and green arrows represent trafficking events that are involved in increasing AMPAR surface expression.